We have now shown that rG-CSF pretreatment in a nonneutropenic canine model of lethal bacterial peritonitis improves cardiovascular function and survival. These improvements are associated with decreases in circulating blood bacteria counts and endotoxin and tumor necrosis factor levels. It is unclear from these studies whether G-CSF is capable of accelerating endotoxin clearance directly. In order to determine this, we performed additional studies and evaluated the effects of rG-CSF pretreatment in animals challenged with endotoxin alone. In these studies we have shown that G-CSF pretreatment does in fact accelerate endotoxin clearance. In contrast to what we saw with bacterial infection however, in the setting of endotoxin challenge alone, G-CSF was associated increases in pulmonary arterial pressures, evidence of possible lung injury. In subsequent studies, using monoclonal antibodies directed against the leukocyte CD18 adhesion complex, we showed that this surface receptor did not participate in the increased endotoxin clearance seen with G-CSF. However, this MAb did result in reductions in the pulmonary arterial hypertension seen with endotoxin and G-CSF. To better determine whether this represents an effect of MAb specifically on G-CSF or whether it is related to an effect of MAb on endotoxin alone, a final set of studies are being conducted to evaluate the effects of CD18 directed MAb in the setting of endotoxin challenge. These findings may help clarify the mechanisms underlying the pulmonary toxicity now being observed both clinically and in animal models of acute lung injury with G-CSF.